Sleep and Sleep Regulation in Normal and Prion Protein-Deficient Mice

Abstract

Mice are the preferred mammalian species for genetic investigations of the role of proteins. The normal function of the prion protein (PrP) is unknown, although it plays a major role in the prion diseases, including fatal familial insomnia. We investigated its role in sleep and sleep regulation by comparing baseline recordings and the effects of sleep deprivation in PrP knockout mice (129/SV) and wild-type controls (129/SV ϫ C57BL/6), which are the mice used for most gene targeting experiments and whose behavior is not well characterized. Although no difference was evident in the amount of vigilance states, the null mice exhibited a larger degree of sleep fragmentation than the wild-type with almost double the amount of short waking episodes. As in other rodents, cortical temperature closely reflected the time course of waking. The increase of slow-wave activity (SWA; mean EEG power density in the 0.25-4.0 Hz range) at waking to nonrapid eye movement (NREM) sleep transitions was faster and reached a lower level in the null mice than in the wild-type. The contribution of the lower frequencies (0.25-5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance states, and the distinction between NREM sleep and REM sleep was most marked in the theta band. After the sleep deprivation, SWA was increased, but the changes in EEG power density and SWA were more prominent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.

Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation

“…These data confirm the results obtained in mice of other lines (Franken et al, 2001;Lena et al, 2004;Tobler et al, 1997), and are consistent with those in humans after one night of sleep deprivation (Borbely et al, 1981;Dijk and Beersma, 1989).…”

“…These rhythms are classically observed in mice of various genetic backgrounds (Boutrel et al, 1999;Boutrel et al, 2002;Franken et al, 1998;Lena et al, 2004;Tobler et al, 1997). The comparison between H and NH mice confirms and extends our previous data (El Yacoubi et al, 2003).…”

“…For this purpose, animals were continuously observed and objects (pencil, pieces of paper, plastic tubes) were introduced into the cage to disturb the mouse as soon as it engaged in a sleeping posture (Lena et al, 2004;Tobler et al, 1997). At the end of the deprivation period, animals were left to sleep freely and were recorded for 18 h (from 1300 to 0700 the next morning).…”

“…Polygraphic recordings were scored visually every 15 s epoch as wakefulness (W), SWS or REM sleep following classical criteria (Lena et al, 2004;Tobler et al, 1997), using the Somnologica s software (Flaga, Reykjavik, Island). SWS was subdivided into light (SWS 1 ) and deep (SWS 2 ) according to the criteria defined for rats (Neckelmann and Ursin, 1993) and adapted to mice: when delta waves were present during less than 50% of the epoch, it was scored as SWS 1 , and when this percentage was higher than 50%, as SWS 2 .…”

“…During recovery from sleep deprivation, this homeostatic drive notably causes an increase of slow wave activity (SWA) assessed by quantitative EEG measures, in humans (Borbely et al, 1981), rats (Borbely et al, 1981;Tobler and Borbely, 1990), as well as mice (Franken et al, 2001;Lena et al, 2004;Tobler et al, 1997). The magnitude of SWA depends on the duration of prior waking (Tobler and Borbely, 1990), which suggests that SWA is a marker for sleep intensity (Borbely et al, 1981).…”